Inclusion Criteria:

1. Males, age 18-75 years old;
2. BMI 19-35 kg/m2;
3. Good health;
4. Systolic BP 90-140 mmHg, diastolic BP 50-90 mmHg, resting HR 45-90 bpm without medication;
5. Clinical chemistry profile within 2x normal range without medication;
6. Urinalysis including urinary creatinine within 2x normal limits;
7. OA confirmed by radiographs obtained within the past 20 years and diagnosed according to ACR guidelines; subjects must qualify as ACR global functional status I, II, or III (excluding IV) and Kellgren-Lawrence grade 1, 2 or 3 (excluding grades 0 and 4);
8. Subjects must have had chronic pain for ≥3 months from OA;
9. Subjects must have been receiving stable oral doses of NSAIDs or COX-2 inhibitors at least 3 days per week for one month or longer;
10. Subjects may take paracetamol ≤2g/day) for breakthrough pain;
11. During the washout period, the average daily pain intensity (DPI) score must be between 4 and 8 on a 0-10 numerical rating scale for at least 3 days, and no greater than 9 for more than 1 day, in the last 5 days prior to randomization per Baseline pain diary;
12. Subjects must be able to read, understand and follow the study instructions;
13. Subjects and their sexual partners must agree to use double barrier contraception during the study period and for 2 months afterward.

Exclusion Criteria:

1. Use of any analgesics except the study medication or paracetamol;
2. Presence or history of peripheral edema within the past 5 years;
3. History of congestive heart failure;
4. Use of chemotherapy agents or history of cancer within five years prior to the screening visit;
5. History of bacterial or viral infection requiring treatment with antibiotics, antivirals, or anti-retrovirals within 3 months of study;
6. Use of drugs which are P450 3A4 inducers or inhibitors within the past 30 days;
7. Use of prescribed systemic or topical medications or any dietary aids or foods that are known to modulate drug metabolizing enzymes within 14 days of dose administration;
8. Difficulty in swallowing oral medications;
9. Subjects with gout, pseudogout, inflammatory arthritis, Paget's disease of bone, chronic pain syndrome, fibromyalgia, or another major joint disease;
10. Subjects requiring knee or hip arthroplasty within 2 months of screening or anticipating any need for a surgical procedure on the index joint during the study;
11. Subjects who have had surgery on the affected joint within one year prior to the study and subjects with a prosthesis at the index joint;
12. Use of systemic corticosteroids within 2 months of screening, or intra-articular viscosupplementation within the past 6 months;
13. History of seizure disorder;
14. Use of antidepressants or anticonvulsants for any reason including for chronic pain within 2 months of screening;
15. Serious psychosocial co-morbidities;
16. Cognitive or psychiatric disorders, or daytime use of medications that could diminish compliance with study procedures, including maintenance of a daily pain and symptom diary and accurate dosing of study medication;
17. Use of anticoagulants within 2 weeks of screening;
18. Use of any medications that will affect pain perception;
19. History of drug or alcohol abuse within one year prior to screening;
20. Use of any other investigational drug within 1 month prior to randomization;
21. Active gastrointestinal, renal, hepatic, or coagulant disorder within 1 month prior to randomization;
22. Esophageal or gastroduodenal ulceration within 1 month prior to randomization;
23. Hypersensitivity to NSAIDs, sulfonamides, COX-2 inhibitors, or carbonic anhydrase inhibitors;
24. History of nasal polyps, bronchospasm or urticaria;
25. Known allergy or hypersensitivity to sulfa drugs;
26. Family history of significant cardiac disease;
27. Occult blood in stool.